1. Field of the Invention
The present invention relates to an improved process for the preparation of xcex2,xcex3,xcex4-allenic and/or xcex1,xcex2,xcex3,xcex4-conjugated di-unsaturated ketones by the reaction of propargyl alcohols with enol ethers in the presence of an acid catalyst at elevated temperature.
2. Discussion of the Background
A range of xcex2,xcex3,xcex4- and xcex1,xcex2,xcex3,xcex4-unsaturated ketones constitute valuable intermediate products for the preparation of vitamins E, A, K1 and carotinoids.
Reaction of an unsaturated alcohol and an enol ether was described for the first time by Marbet and Saucy in Chimia 14 (1960), pages 362 to 363. Methyl or ethyl is isopropenyl ether, which have boiling points of 34xc2x0 C. and 61xc2x0 C. respectively, are often utilized in the Saucy-Marbet reaction. The reaction temperature of the Saucy-Marbet reaction is, however, higher than the boiling points of the ethers. In order to reach the reaction temperature necessary for achieving high conversions and adequate space-time yields, the reaction is carried out either in the presence of a solvent or in solvent-free manner under pressure.
DE 1 230 783 describes a process for the preparation of polyene ketones and their isomerization products from secondary alcohols in the presence of acid catalysts such as, for example, sulfuric or phosphoric acid.
U.S. Pat. No. 3,029,287 and the publication by R. Marbet and G. Saucy, Helv. Chim. Acta (1967) 50, 1158-1167 describe a process for the preparation of xcex2,xcex3,xcex4-unsaturated ketones by the reaction of propargyl alcohols with enol ethers in the presence of an acid catalyst. The reaction times required in order to achieve complete conversion of the tertiary propargyl alcohol are, however, in excess of 15 hours according to this publication. These long reaction times necessitate high reaction volumes when the process is translated to the industrial scale, hence giving rise to high capital costs.
The reaction of dehydrolinalool with isopropenyl methyl ether catalyzed by p-toluenesulfonic acid to obtain a mixture of 6,10-dimethyl-4,5,9-undecatrien-2-one and pseudoionone isomers is disclosed in CS 235228. The reaction times required in order to achieve complete conversion of the dehydrolinalool are 17 hours at 100xc2x0 C. The long reaction times are disadvantageous in this process.
It was described in DE 199 49 796.6 that the Saucy-Marbet reaction is catalyzed efficiently by aliphatic sulfonic acids or sulfonic acid salts, with markedly shortened reaction times in comparison to prior art processes. The reaction times are from 6 to 8 hours. In accordance with this process the reaction is carried out in the presence of a suitable solvent so that the necessary reaction temperature can be reached. However, yields decrease when working under pressure in the absence of the solvent. Carrying it out the process in the presence of a solvent moreover gives rise to an increased plant cost for isolating and working up the product.
Accordingly, an object of the invention is to improve the reaction between an unsaturated alcohol and an enol ether in a Saucy-Marbet reaction to obtain unsaturated ketones so as to enable the reaction to be carried out in highly selective manner and with markedly reduced reaction times. A further object of the invention is the achievement of the aforementioned aims without the need to work with additional reaction solvents.
The invention provides a process for the preparation of xcex2,xcex3,xcex4-unsaturated ketones and/or xcex1,xcex2,xcex3,xcex4-unsaturated ketones by the reaction of an unsaturated alcohol with an enol ether or mixture of enol ethers, with formation of ketals as a by-product, at temperatures of from 50xc2x0 C. to 200xc2x0 C., in the presence of an acid catalyst.
The process according to the invention is characterized in that one or all of the reagents is/are heated to reaction temperatures of from 50xc2x0 C. to 200xc2x0 C. before the acid catalyst is added.
One aspect of the invention is a process for the preparation of xcex2, xcex3, xcex4 unsaturated ketones corresponding to the general Formula (IA) and/or xcex1, xcex2, xcex3, xcex4-unsaturated ketones corresponding to the general Formula (IB) 
in which
R1 and R2 are hydrogen, a C1-C20 alkyl radical which is optionally substituted with oxygen-containing groups and may be saturated or unsaturated, branched or unbranched, or a C1-C20 alkylaryl radical, whereby the radicals R1 and R2 may also together form a 5- or 6-membered ring;
R3 and R5 are hydrogen or a C1 to C4-alkyl radical, preferably hydrogen, and
R4 is a hydrogen or a C1 to C4-alkyl radical;
or mixture thereof,
by the reaction of an unsaturated alcohol corresponding to the general Formula II 
in which
R1, R2 and R3 denote the same as indicated above, with an enol ether corresponding to the general Formula III 
in which
R4 is hydrogen or a C1- to C4-alkyl radical, preferably a methyl radical;
R5 denotes the same as indicated above, and
R6 is a C1- to C4-alkyl radical, preferably a methyl radical;
with formation, as a by-product, of ketals corresponding to the Formula IV in which R4, R5 and R6 denote the same as indicated above 
xe2x80x83at temperatures of from 50xc2x0 C. to 200xc2x0 C., in the presence of an acid catalyst.
The process according to the invention may, for example, be carried out in the following variants:
A. an unsaturated alcohol corresponding to the Formula II is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst to a temperature of between 50xc2x0 C. and 200xc2x0 C., preferably between 60xc2x0 C. and 170xc2x0 C., particularly preferably between 80xc2x0 C. and 130xc2x0 C. When the desired reaction temperature is reached, with the pressure having risen in the vessel, an enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III, an acid catalyst, are dispensed-in, in mixed or separate manner, in continuous manner or portion-wise; or
B. an unsaturated alcohol corresponding to the Formula II as a mixture with an enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst to a temperature of between 50xc2x0 C. and 200xc2x0 C., preferably between 60xc2x0 C. and 170xc2x0 C., particularly preferably between 80xc2x0 C. and 130xc2x0 C. When the desired reaction temperature is reached, with the pressure having risen in the vessel, the acid catalyst is then dispensed-in in a continuous manner or portion-wise; or
C. the enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst and the unsaturated alcohol to a temperature of between 50xc2x0 C. and 200xc2x0 C., preferably between 60xc2x0 C. and 170xc2x0 C., particularly preferably between 80xc2x0 C. and 130xc2x0 C. When the desired reaction temperature is reached, and the pressure within the vessel has increased, an acid catalyst and an unsaturated alcohol corresponding to the Formula II, are then added, in mixed or separate manner, in continuous manner or portion-wise,
In each of A, B and C described above, it is possible to introduce as an initial charge, and then to heat to a temperature of between 50xc2x0 C. and 200xc2x0 C., a portion of the reagent or reagents in the absence of the acid catalyst, and then to add thereto the remainder of the reagent or reagents and the acid catalyst in continuous manner or portion-wise.
In a farther aspect of the invention, a liquid base or a basic solution which is able to form a salt which has acid properties xe2x80x9cin situxe2x80x9d with the acid catalyst, may be added into the initial reaction mixture, in addition to the dispensing-in portion-wise or in continuous manner of the acid catalyst, at the necessary reaction temperature.
When the reaction is carried out under the conditions according to the invention only low concentrations of by-products, in particular high-boiling by-products, other than the desired ketal are formed. The ketal is a starting material for the preparation of the enol ether corresponding to the Formula III and can be recycled for this purpose. The reaction of the process according to the invention proceeds in highly selective manner, and despite high reaction rates, excellent yields are obtained, even in the absence of a solvent. Working-up in particular is substantially facilitated by the achievement of high selectivities such as, for example, at least 85%, preferably at least 90% and particularly preferably at least 93%.
The space-time yields of the process according to the invention are consequently substantially higher than those of the prior art.
Preferred unsaturated alcohols corresponding to the Formula II in the process according to the invention are those in which
R1 stands for a C1-C20 alkyl radical which may be saturated or unsaturated, branched or unbranched, a C1-C-20 aryl radical, or an arylalkyl radical, and
R2 stands for a C1 to C4 alkyl radical, in particular a methyl radical,
R3 stands for hydrogen.
The following are examples of suitable propargyl alcohols:
3-methyl-1-butyn-3-ol;
3,7-dimethyl-6-octen-1-yn-3-ol (dehydrolinalool);
3,7-dimethyl-5-octen-1-yn-3-ol;
3,7-dimethyl-4-octen-1-yn-3-ol;
3,7-dimethyl-1-octyn-3-ol(hydrodehydrolinalool);
3,7,11-trimethyl-6,10-dodecadien-1-yn-3-ol (dehydronerolidol);
3,7,11-trimethyl-6-dodecen-1-yn-3-ol;
3,7,11-trimethyl-1-dodecyn-3-ol(hydrodehydronerolidol);
1-ethynyl-1-cyclohexanol; and
1-ethynyl-2,2,6-trimethyl-1-cyclohexanol.
As enol ethers corresponding to the Formula III, compounds in which
R4 is hydrogen or a methyl radical,
R5 is hydrogen, and
R6 is a methyl radical or ethyl radical
are preferably considered.
The following are examples of suitable enol ethers: isopropenyl methyl ether, isopropenyl ethyl ether, isopropenyl propyl ether, isopropenyl butyl ether, isopropenyl isobutyl ether, 2-methoxy-1-butene, 2-ethoxy-1-butene, 2-propoxy-1-butene, 3-butoxy-1-butene, 2-m ethoxy-2-butene, 2-ethoxy-2-butene, 2-methoxy-1-pentene, 2-ethoxy-1-pentene, 2-methoxy-2-pentene, 2-ethoxy-2-pentene, 3-methoxy-3-pentene, 3-ethoxy-2-pentene, in particular isopropenyl methyl ether.
On an industrial scale isopropenyl methyl ether is frequently preferred for reasons relating to both economics and process engineering because the dimethoxypropane formed from it can be readily recovered by distillation from the reaction mixture and re-utilized for the preparation of isopropenyl methyl ether.
The reaction takes place at temperatures of between approx. 50xc2x0 C. and 200xc2x0 C., preferably between 60xc2x0 C. and 170xc2x0 C., particularly preferably between 80xc2x0 C. and 130xc2x0 C. A particularly high reaction rate such as, for example, less than 5 hours, preferably less than 4 hours, particularly preferably less than 3 hours, is achieved with no observable impairment of the selectivity, when the reaction is carried out at different temperature levels which are adjusted dependent on the degree of conversion of the unsaturated alcohol. At the beginning of the reaction a temperature is normally adjusted which is approximately 10xc2x0 C.-30xc2x0 C. lower than the temperature level at the end of the reaction.
The reaction may be carried out in a batch, semi-batch or continuous process. The reaction may furthermore be carried out in pressure-less manner but also under pressure. In the case of a pressure reaction the reaction takes place within the pressure range 1 to 20 bar, preferably 1 to 10 bar.
The molar ratio of the unsaturated alcohol corresponding to the Formula II and the enol ether corresponding to the Formula III is generally between 1:2 and 1:10, preferably 1:2.05 to 1:5, particularly preferably 1:2.05 to 1:3.5. The excess enol ether may be recovered by distillation after the reaction has ended.
The following serve as catalysts in the process according to the invention: mineral acids such as, for example, sulfuric or phosphoric acid and salts thereof, strong organic acids such as oxalic acid, trichloroacetic acid, p-toluic acid, as well as Lewis acids such as zinc chloride or boron trifluoride etherate, and aliphatic sulfonic acids and salts of the corresponding sulfonic acids having acid properties are particularly preferred.
The following are examples of suitable aliphatic sulfonic acids: methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, pentanesulfonic acid, hexanesulfonic acid, chloromethanesulfonic acid, in particular methanesulfonic and ethanesulfonic acid.
The following are examples of suitable sulfonic acid salts: pyridinium p-toluolsulfonate, tetramethylammonium p-toluenesulfonate, pyridinium methanesulfonate, pyridinium ethanesulfonate, in particular pyridinium p-toluolsulfonate and pyridinium methanesulfonate, which may optionally form in situ from the corresponding acid and the corresponding base.
A solvent such as acetone, methyl isobutyl ketone, methyl isopropyl ketone, ethanoic acid, formic acid, propionic acid, 2-ethylhexanoic acid may be used as a solvent for the catalysts. It is, however, also possible to utilize the unsaturated alcohol corresponding to the general Formula II, in which R1 and R2 denote the same as indicated above. The quantity of the solvent for the acid catalyst is not critical and is typically from 5 to 100 times the quantity of the catalyst.
The Saucy-Marbet reaction may be carried out with or without reaction solvent. Reactions which are carried out in solvent-free manner are preferred. The following may be utilized as suitable reaction solvents within the scope of the present invention: hydrocarbons, for example hexane, heptane, octane, toluene and xylene; and ketones, for example isobutyl methyl ketone, diethyl ketone isophorone, and dimethoxypropane. If utilized, the reaction solvent may be used in quantities of from 0.5 to 10 times the quantity of the propargyl alcohol utilized. The reaction may be carried out in discontinuous manner but also in continuous manner.
A cascade of stirred-tank reactors or tubular reactors designed for reactions under pressure, or a cascade of corresponding stirred-tank reactors and tubular reactors is then used as the reaction vessel.
The xcex1,xcex2,xcex3,xcex4- and xcex2,xcex3,xcex4-unsaturated ketones desired as intermediate products for vitamin E, vitamin A, carotinoids and fragrances may be prepared by the process of the invention. The product IA or mixture of IA and IB may be converted by basic isomerization to xcex1,xcex2,xcex3,xcex4-dienones corresponding to the general Formula IB, in which R1, R2, R3 and R4 denote the same as indicated above, the latter may be used as important intermediates for vitamin A, E, K1 and carotinoids.
However, the allene ketones which arise may also be hydrogenated to saturated ketones corresponding to the general Formula V 
in which R1, R2, R3 and R4 denote the same as indicated above. The saturated ketones can be important intermediates for vitamin E synthesis.
The Examples which follow serve to describe specific embodiments of the invention and are not intended to limit the invention.